DESCRIPTION: This proposal examines the ability of vitamin-D and its derivatives to regulate cell growth in colonic cancer. The applicant and his coworkers have shown that F6-D3, a fluorinated, non-calcemic analog of 1-alpha,25 (OH)2-D3 reduced the incidence of colonic adenomas and prevented the development of adenocarcinomas in experimental models. In order to understand the role of vitamin D3 in colonic normal and abnormal function, studies are proposed in normal rat colon and in CaCo-2 cells, a cell line derived from a human colonic adenocarcinoma. The cells exhibit similar signal transduction mechanisms and respond in similar fashion to vitamin D as their normal counterparts. Previous studies have shown that vitamin D and F6-D3 decreased cellular proliferation in these cells, while more recent studies have shown that they induce growth arrest in the G1 phase of cell cycle and bring about apoptosis. Accordingly the specific aims of the proposal are to characterize the mechanisms involved in inhibition of cellular proliferation in CaCo-2 cells and the actions of the secosteroids in inducing apoptosis.